A good enzyme model should not only possess appropriate functional groups properly arranged in space but should also possess a cavity into which the substrate molecule can fit. Among the "simple" organic molecules potentially capable of providing these capacities are those that form clathrates. The present study involves certain clathrate-forming (1,1,1,1) metacyclophanes synthesized by the condensation of p-substituted phenols and formaldehyde. The cyclic tetramers that are produced are held in a "cone" conformation by hydrogen bonding and are called calixarenes (Gr. calix, basin). From 4-phenylphenol, for example, a calixarene is obtained which contains a deep cavity and which can carry a variety of functional groups (e.g. OH, CO2H, NH2, etc.) on the upper rim of the calix. The proposed research involved an investigation of methods for synthesizing calixarenes with various sizes and shapes of cavities, calixarenes with various groups on or near the upper rim of the calix, calixarenes with various degrees of conformational mobility, chiral calixarenes, bridged calixarenes, and homocalixarenes. The products from these syntheses are to be studied for their chemical, physical, spectral, conformational, and catalytic properties - particularly their potential as enzyme models. For example, the aldolization of dihydroxyacetone phosphate (DHAP) is to be studied via a calixarene prepared from 4-phenylphenol, containing three-atom bridges between the 3' and 5' positions of each of the biphenyl rings, and three OH groups and one NH2CH2CH2O group on the upper rim of the calix. It is postulated the the cavity of the calixarene will form an inclusion complex with DHAP, that the NH2 group on the rim will form a Schiff base with DHAP, and that the OH groups (in the phenoxide form) will abstract an alpha-H from DHAP to form the anion (the rate-determining step in the aldolization). Numerous other reactions which should be facilitated by complex formation are also to be studied using the calixarenes. It is anticipated that calixarenes will find practical uses as selective catalysts and in pharmaceutical applications.